School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
Cell Immunol. 2020 Dec;358:104239. doi: 10.1016/j.cellimm.2020.104239. Epub 2020 Oct 17.
Roxithromycin (ROX) is a macrolide antibiotic with a variety of immunological effects. Mast cells (MCs) play a key role in host defense, mediating hypersensitivity and pseudo-allergic reactions. Mas-related G protein-coupled receptor X2 (MrgprX2) is the main receptor related to pseudo-allergy. In this study, we investigated the anti-pseudo-allergy effect of ROX and its underlying mechanism. The effects of ROX on passive cutaneous anaphylaxis (PCA) and active systemic allergy were examined, degranulation, Ca influx, and cytokine release were studied in vivo and in vitro. Interactions between ROX and MrgprX2 protein were also detected through surface plasmon resonance. The PCA and active systemic allergy induced by compound 48/80 were inhibited by ROX. An intermolecular interaction was detected between the ROX and MrgprX2 protein. In conclusion, ROX could inhibit pseudo-allergic reactions, and this effect involves the Ca/PLC/IP3 pathway of MrgprX2. This study provides new insight into the anti-pseudo-allergy effects of ROX.
罗红霉素（ROX）是一种具有多种免疫作用的大环内酯类抗生素。肥大细胞（MCs）在宿主防御中起关键作用，介导过敏反应和类过敏反应。与类过敏反应相关的主要受体是与 Mas 相关的 G 蛋白偶联受体 X2（MrgprX2）。在本研究中，我们研究了 ROX 的抗类过敏作用及其潜在机制。通过体内和体外实验研究了 ROX 对被动皮肤过敏（PCA）和主动全身过敏的影响、脱颗粒、Ca 内流和细胞因子释放。还通过表面等离子体共振检测了 ROX 与 MrgprX2 蛋白之间的相互作用。ROX 可抑制 48/80 诱导的 PCA 和主动全身过敏反应。检测到 ROX 与 MrgprX2 蛋白之间存在分子间相互作用。总之，ROX 可抑制类过敏反应，这种作用涉及 MrgprX2 的 Ca/PLC/IP3 途径。本研究为 ROX 的抗类过敏作用提供了新的见解。
